SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

Huntingtons disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies

Acoustic transmission through compound subwavelength slit arrays

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The angular dependence of the transmission of sound in air through four types of 2D slit-arrays formed of aluminium slats is explored, both experimentally and numerically. For a simple, subwavelength periodic slit-array, it is well known that Fabry-Perot-like wave-guide resonances, supported by the slit-cavities, hybridising with bound acoustic surface waves, result in ‘Enhanced Acoustic Transmission’ at frequencies determined by the length, width and separation of each slit-cavity. We demonstrate that altering the spacing or width of some of the slits to form a compound array (i.e. an array having a basis comprised of more than one slit) results in sharp dips in the transmission spectra, that may have a strong angular dependence. These features correspond to ‘phase resonances’, which have been studied extensively in the electromagnetic case. This geometry allows for additional near-field configurations compared to the simple array, whereby the field in adjacent cavities can be out-of-phase. Several types of compound slit-array are investigated; one such structure is optimised to minimise the effect of boundary-layer loss mechanisms present in each slit cavity, thereby achieving a deep, sharp transmission minimum in a broad maximumThe authors would like to thank the UK Ministry of Defence’s Defence Science and Technology Laboratorty (DSTL) for their financial support and permission to publis

Comparison of surgical indications and short- and long-term complications in 56 cats undergoing perineal, transpelvic or prepubic urethrostomy

Objectives The aim of this study was to compare indications, complications and mortality rates for perineal urethrostomy (PU), transpelvic urethrostomy (TPU) and prepubic urethrostomy (PPU). Methods A retrospective review of, and follow-up owner questionnaire for, cats undergoing urethrostomy between 2008 and 2018, at a single referral hospital, were performed. Results Fifty-six cats underwent urethrostomy (PU, n = 37; TPU, n = 8; PPU, n = 11). The presenting problem was significantly associated with urethrostomy technique (P <0.001). For PU cats, feline idiopathic cystitis (FIC; n = 21 [56.7%]) was the most common problem, whereas for PPU cats, trauma (n = 9 [81.8%]) was most common (P <0.001). Urethrostomy technique was associated with imaging diagnosis (P <0.001) of the urethral lesion. Most PU cats had no diagnostic imaging lesion (n = 15 [40.5%]) or obstructive calculi or clots (n = 10 [27.0%]), and all PPU cats had urethral rupture. Ten (90.9%) PPU cats had a pelvic lesion, while 21 (56.7%) PU cats had a penile lesion. TPU cats had a range of presenting problems and imaging diagnoses. Short- and long-term complications were reported in 33/55 (60.0%) and 11/30 (36.7%) cats, respectively. The number of cats with long-term complications was greater among PPU cats (P = 0.02). Short-term dermatitis (P = 0.019) and long-term incontinence (P = 0.01) were associated with PPU. Short-term mortality was 5.6% and long-term mortality was 13.3%; both were independent of urethrostomy technique. Quality of life post-urethrostomy, across all techniques, was graded as good by 93% of owners. Conclusions and relevance In this study, PU was the most common feline urethrostomy technique indicated for FIC. Short-term urethrostomy complications are common, irrespective of urethrostomy technique. Long-term complications are less frequent but more common with PPU

Low energy photoelectron diffraction analysis at high angular resolution of Cu and Mn/Cu surfaces

X-ray photoelectron diffraction simulations using a real-space approach are Shown to accurately produce the extraordinarily detailed photoelectron diffraction pattern from Cu{111} at an electron kinetic energy of 523.5 eV. These same simulations show that most sensitivity is obtained when using low energy electrons at high angular resolution Structural differences are observed to be greatest around a kinetic energy of similar to 100 eV and many of the features observed in the photoelectron diffraction patterns may be directly related to phenomena observed in low energy electron diffraction patterns from the same Surface. For Cu{100}. simulations of buckled surfaces with a Mn overlayer predict that low energy photoelectron diffraction can easily discriminate chemical and structural differences. Even the effects of the relaxed Surface of Cu{100} is indeed observable along azimuthal scans around a kinetic energy of 100 eV Our results show that low energy photoelectron diffraction is extremely sensitive to changes in Surface Structure If high resolution patterns are acquired. © 2009, American Institute of Physics

The waveguiding of sound using lines of resonant holes

This is the final version. Available on open access from Nature Research via the DOI in this recordThe dispersion of an acoustic surface wave supported by a line of regularly spaced, open ended holes in an acrylic plate, is characterised by precise measurement of its localised acoustic fields. We illustrate the robust character of this surface wave and show its potential for control of sound by the acoustic waveguiding provided by a ring of regularly spaced holes.Defence Science and Technology Laboratory (DSTL

Stable isotope evidence for crustal recycling as recorded by superdeep diamonds

© 2015 Elsevier B.V. Sub-lithospheric diamonds from the Juina-5 and Collier-4 kimberlites and the Machado River alluvial deposit in Brazil have carbon isotopic compositions that co-vary with the oxygen isotopic compositions of their inclusions, which implies that they formed by a mixing process. The proposed model for this mixing process, based on interaction of slab-derived carbonate melt with reduced (carbide- or metal-bearing) ambient mantle, explains these isotopic observations. It is also consistent with the observed trace element chemistries of diamond inclusions from these localities and with the experimental phase relations of carbonated subducted crust. The 18O-enriched nature of the inclusions demonstrates that they incorporate material from crustal protoliths that previously interacted with seawater, thus confirming the subduction-related origin of superdeep diamonds. These samples also provide direct evidence of an isotopically anomalous reservoir in the deep (≥350 km) mantle

Reaching peak emissions

Rapid growth in global CO2 emissions from fossil fuels and industry ceased in the past two years, despite continued economic growth. Decreased coal use in China was largely responsible, coupled with slower global growth in petroleum and faster growth in renewables